Bisphenol phosphorus esters

ABSTRACT

Phosphorus-containing esters of various bis-phenols having germicidal activity. The foregoing esters in combination with certain halogensubstituted carbanilide and anilides display synergistic germicidal activity.

United States Patent Jungermann et al.

BlSPI-IENOL PHOSPHORUS ESTERS Inventors: Eric Jungermann, Chicago; Henry E. Reich, Wilmette, both of Ill.

Assignee: Armour-Dial, Inc., Chicago, 111.

Filed: June 12, 1969 Appl. No.: 832,813

Related U.S. Application Data Continuation-impart of Ser. No. 579,195, Sept. 15, 1966, abandoned.

[451 Apr. 24,1973

[56] References Cited UNITED STATES PATENTS 3,297,631 1/1967 Brown et al. "260/953 X Primary ExaminerLewis Gotts Assistant Examiner-Anton H. Sutto AttorneyCarl C. Batz and Richard G. Harrer [57] ABSTRACT Phosphorus-containing esters of various bis-phenols having germicidal activity.

The foregoing esters in combination with certain halogen-substituted carbanilide and anilides display synergistic germicidal activity.

1 Claim, No Drawings BllSPHENOL PHOSPHORUS ESTERS This application is a continuation-in-part of application Ser. No. 579,195, filed Sept. 15, 1966, now abandoned.

This invention relates generally to anti-bacterial substances and more particularly to soap germicides.

In one specific aspect, the present invention relates to novel phosphorus-containing esters that are useful as soap germicides and to germicidally synergistic compositions incorporating such esters.

Numerous compounds have in the past been investigated for antibacterial activity; and while many substances have exhibited a degree of effectiveness, few have produced the desired results in anything more than certain limited circumstances. Quaternary ammonium compounds, for example, have potent germicidal activity in water solution but are generally incompatible with soap and anionic synthetic detergents. Quaternary ammonium compounds also have proved difficult to disperse uniformly in solid products such as washing powders. Silver ion has exhibited powerful bactericidal properties, but silver ion is unstable to light and hence cannot be employed in products where discoloration from the reduction of silver ion to silver metal would be objectionable. Products such as toilet soap add a further requirement for any germicide that is proposed for use therein, viz. that the germicide must not be harmful to the human skin. Thus, the various known germicides can be useful in special instances but not universally; and it is therefore commercially desirable to have a considerable variety of germicides from which a selection may be made for a given end use.

Accordingly, an important object of the present invention is to provide a new substance for imparting germicidal activity to various products.

A more general object of the invention is to provide a useful but hitherto germicidal chemical reaction product.

Another object of the invention is to provide a novel composition of matter having germicidal activity; and a specific object of the invention is to provide a novel germicidal soap product.

These and other objects and features of the invention will become more apparent from a consideration of the following descriptions.

The phosphorus-containing esters of the invention are produced by the alcoholysis of an alkyl phosphinoyl chloride using a bisphenolic material. These esters are also obtained by partially or completely hydrolyzing the phosphinoly chloride to the corresponding phosphinic acid before reaction with the bisphenolic material. The phosphorus-containing esters which find utility in this invention more specifically comprise the reaction product of a branched chain alkyl phosphinic acid or a branched chain alkyl phosphinoly chloride and an aromatic bis-chlorohydrin. The esterified product of the invention is principally the compound which conforms to the general structural formula:

wherein X is hydrogen or a halogen, X is a halogen, Y represents a divalent alkylene moiety having from one to four carbon atoms or sulfide, the arrow represents a semi-polar bond, and Z is selected from the group consisting of an alkenyl radical containing from six to 12 carbon atoms, or

wherein X X Y and the arrow are as designated above and wherein R is a carbon atom, n is an integer of from two to five and wherein any one or more of the hydrogen (-H) in any RH group can be substituted by an alkyl group of from one to 10 carbon atoms and wherein the total number of carbon atoms in the RH-,. and --RH substituted groups is from six to 12.

The phosphorus-containing esters of the invention may be prepared in a two-step synthesis involving, first, the conversion of a branched chain, unsaturated aliphatic hydrocarbon to the corresponding phosphinoyl chloride and, secondly, the alcoholysis of the acid chloride. Preparation of the phosphinoyl chloride is achieved by the procedure of Jungermann et al, J. Org. Chem., 27, 606 (1962); and preferred starting material include such unsaturated aliphatic hydrocarbons as ldodecene, l-hexene, and 2,4,4-trimethylpentene-2. However, other unsaturated aliphatic hydrocarbons, including other alpha olefins, especially those containing from six to 12 carbon atoms, may be utilized, there being no apparent influence on the germicidal activity of the final material that is a result of the chosen alkyl substituent.

The bisphenolic material employed in the alcoholysis of the phosphinoyl chloride is a bis-aromatic chlorohydrin, and specific compounds contemplated by the invention include:

2,2'-methylenebis(3,5,6-trichlorophenol);

2,2-methylenebis(4,5,6-trichlorophenol); 2,2'-methylenebis(3,4,5-trichlorophenol); 4,4-methylenebis(2,3,6-trichlorophenol); 3,3'-methylenebis(2,4,6-trichlorophenol); 2,2-thiobis(4,6-dichlorophenol); and 2,2'-thiobis(3,S-dichlorophenol).

The phosphorus-containing esters of the invention have utility as germicides, alone and in synergistic combination with various other compounds.

In order to describe the invention more fully, the following specific examples are given without, however, limiting the invention to the precise details set forth except as required by the appended claims.

EXAMPLE I A phosphorus-containing ester of the invention was made by the following laboratory procedure:

To a l-liter, 4-necked flask provided with a thermometer, a stirrer, a dropping funnel and a reflux condenser, there was charged a solution of 19.4 grams (0.345 moles) of potassium hydroxide dissolved in ml. of methanol together with 142 grams (0.345 moles) of 2,2'-methylenebis(3,5,6-trichlorophenol) dissolved in 200 ml. of methanol. The resulting, clear orange mixture was heated to 45 C. Previously, a phosphinoyl chloride prepared from 2,4,4-trimethylpentene-2 by the method of Jungermann et al, supra, had been prepared; and a mixture of 67.0 grams (0.345 moles) of the phosphinoyl chloride, dissolved in 50 ml. of methanol, was added dropwise to the heated orange mixture in the flask, the dropwise addition proceeding over a period of about twenty minutes. After the addition of the phosphinoyl chloride, the mixture was heated to reflux for three hours, cooled, filtered to remove the precipitated potassium chloride salt, and stripped free of volatiles. The crude tan-colored solid residue was slurried with 100 ml. of warm methylene chloride and filtered to yield 170 grams of a white solid having a melting point of 274275 C.

The solid material produced by the foregoing synthesis was tested for germicidal activity. The results are set forth in Table I given hereinafter. The ester produced by this procedure had the structure:

CH3 CH3 CH l C CHs Q Cl 01 c1 c1 EXAMPLE II The procedure outlined for Example I was repeated with the exception that 0.345 moles of a phosphinoly chloride derived from l-dodecene was substituted for the phosphinoyl chloride derived from 2,4,4-trimethylpentene-2.

The melting point of the purified solid was determined to be 240-243 C. whereas the germicidal activity of the product was determined, the results being set forth in Table I below. This ester had the following structure 5 c1 OH 01 C) It is possible that this ester had the structure:

OF-P 6 Cl OH C1 Cl Cl Cl Cl EXAMPLEIII The general procedure of Example I was repeated a third time using a phosphinoly chloride derived from I- hexene in a stoichiometrically equivalent amount to the phosphinoyl chloride specified in Example I.

10 Cl OH C1 Cl Cl Cl Cl EXAMPLE IV A phosphorus-containing ester was produced from 2,2-thiobis(3,5-dichlorophenol) by mixing 32.4 grams of that compound with l 1.2 grams of potassium hydroxide, 200 ml. of ethanol and 20 grams of the phosphinoyl chloride prepared by the method of Jungermann ct al, supra, using a mixture of l-nonene, ldecene and l-undecene as the starting material. The resultant mixture was refluxed for three hours, cooled and distilled to remove the ethanol. The resulting white solid was water-washed and dried. Its melting point was determined to be 257-260 C.; and the germicidal activity of this ester was determined, the results being set forth in Table I. A mixture of products resulted having 30 the following structure:

III

and

O+PCH=CH(CH2)7CHI (:1 OH 01 I I l l l 1 c1 c1 1 ct and 04-1 r:H=crr(cH.ncrn 31 on c1 -Q c1 c1 (:1 :1

Germicidal activity was determined by a modified agar streak method. In particular, the test materials were incorporated in a soap solution at the level of 1,000 p.p.m. The soap utilized was a neutral white toilet soap containing about 20 percent by weight sodium coconut oil soap and 80 percent by weight sodium tallow soap. Varying amounts of the soap solutions containing the esters of the invention were thoroughly dispersed in measured amounts of liquid nutrient agar at various concentrations ranging from 0.05 to 20 p.p.m. Plates were then poured, solidified and streaked with a standard 4mm. loopful of a 24-hour broth culture of Staphylococcus aureus strain F.D.A. No. 209.

After incubation for 24 hours at 37 C. the bacteriostatic endpoint was determined. This endpoint represents the concentration of test material in p.p.m. necessary to inhibit all growth of the inoculant organism. The comparative endpoints of the esters of Examples I-IV thus determined are set forth in Table I as follows:

TABLE I Olefinic Moiety Melting Bacteriostatic Derived From Point End Point Ex. i 2,4,4-trimethyl- 274-275 0.7 p.p.m.

pentene-Z Ex. ll l-dodecene 240-243 0.5

Ex. Ill Lhexene 293-294 0.5

Ex. IV mixture of l-nonene, 257 260 1-5 ldecene and l-undecene The phosphorus-containing esters of the invention have antibacterial activity alone, as described hereinabove, and in synergistic combination with certain halogen-substituted aromatic primary and secondary amines. In the latter regard, certain carbanilides are of particular utility, and anilides of certain fatty acids have also proved to be useful. The following examples illustrate such synergistic combinations.

EXAMPLES V -VII TABLE II Bacter- Binary Mixture iostatic Single Component (lzl weight ratio) end point Example IV [-5 ppm 3,4,4-

trichloroacarbanilide 0.2 3,4',5-

tribromosalicylanide 0.7 4,4'-dichloro-3 0.07 -(trifluorornethyl) carbanilide Example lV/ 3,4,4-

trichlorocarbanilide 0.050.07 Example lV/ 3,4,5-

tribromosalicylanilide 0.5-1.0 Example IV/ 4,4'-dichloro-3- (trifluoromethyl)carbanilide 0.05-0.07

EXAMPLES VIII XIV A phosphorus-containing ester of the present invention was prepared using the method of Example I and employing a mixture of alpha olefins containing from 7 to 9 carbon atoms as a starting material for the phosphinoyl chloride synthesis. The germicidal activity of the resultant material alone (Example VIII) and its germicidal activity in combination with other substances (Examples IX-XIV was determined. The results are set forth in Table III. It is apparent from the data in Table III that the ester of Example VIII is germicidally synergistic with 3,4,4'-trichlorocarbanilide and with pelargonyl-3,4-dichloroanilide.

TABLE III Bacter- Binary Mixture iostatic Single Component (1:1 weight ratio) End Point Example Vlll 0.5-0.6

p.p.m. 3,4,4-

trichlorocarbanilide 0.2 3,4',5-

tribromosalicylanilide 0.5-0.7 4,4'-dichloro-3 (trifiuoromethyl carbanilide 0.07 Pelargonyl-3A- dichloroanilide 1.0 1-(3,4-

dichlorophenyl)-3-noctylurea 0.2-0.3

Example Vlll/ 3,4,4'-

trichlorocarbanilide 0.06-0.07 Example VIll/ 3,4',5-

tribromosalicylanilide 0.4 Example Vlll/ 4,4'-dichloro-3- (trifluoromethyl)carbanilide 0.06 Example VIII/ pelargonyl 3,4-

dichloroanilide 0.2 Example Vlll/ 1-(3,4-

dichlorophenyl)-3-n-octylurea 0.090.l

EXAMPLE XV In addition, the phosphorus-containing ester of Example l was studied for its germicidal effectiveness in combination with various proportions of N-lauroyl-3 ,4- dichloroanilide. The results are set forth in Table IV below; and it is apparent that mixtures of the ester and the analide are germicidally synergistic.

Determination of the safety of the phosphorus-containing esters of the invention for contact with the human skin was made using the ester of Example I at the 2 percent level by weight in a soap containing 20 percent by weight sodium coconut oil soap and percent by weight sodium tallow soap. Panel tests were conducted with forty-four individuals, each of whom used the test soap product as a personal cleansing product for a period of at least one week. The panel members were instructed to use the test soap product for all underarm washing. At the end of the test, no adverse reports were made by any of the panel members, and the test soap product was found to be generally equivalent to a commercial deodorant soap with respect to the suppression of body odors.

The foregoing detailed descriptions have been given for clarity of disclosure and completeness of understanding only; and no unnecessary limitation should be implied therefrom, as modifications of the invention and related utilities will be apparent to those skilled in the art and therefore within the scope of the appended claims.

What is claimed is:

l. A compound whose general structure is selected from the group consisting of wherein X is selected from the group consisting of hydrogen, chlorine and bromine, X, is a halogen, Y is a divalent alkylene moiety having from one to four carbon atoms or sulfide, the arrow represents a semi-polar bond, Z is an alkenyl radical containing from six to 12 carbon atoms, R is a carbon atom, n is an integer of from two to five and wherein any one or more of the hydrogens (-H) in any RH group can be substituted by an alkyl group of from one to 10 carbon atoms and wherein the total number of carbon atoms in the RH; and RH substituted groups is from six to 

